Application of tissue-scale tension to avian epithelia in vivo to study multiscale mechanical properties and inter-germ layer coupling.

As cross-disciplinary approaches drawing from physics and mechanics have increasingly influenced our understanding of morphogenesis, the tools available to measure and perturb physical aspects of embryonic development have expanded as well. However, it remains a challenge to measure mechanical properties and apply exogenous tissue-scale forces in vivo, particularly for epithelia. Exploiting the size and accessibility of the developing chick embryo, here we describe a simple technique to quantitatively apply exogenous forces on the order of ~1-100 µN to the endodermal epithelium. To demonstrate the utility of this approach, we performed a series of proof-of-concept experiments that reveal fundamental and unexpected mechanical behaviors in the early chick embryo, including mechanotype heterogeneity among cells of the midgut endoderm, complex non-cell autonomous effects of actin disruption, and a high degree of mechanical coupling between the endoderm and adjacent paraxial mesoderm. To illustrate the broader utility of this method, we determined that forces on the order of ~ 10 µN are sufficient to unzip the neural tube during primary neurulation. Together, these findings provide basic insights into the mechanics of embryonic epithelia in vivo in the early avian embryo, and provide a useful tool for future investigations of how morphogenesis is influenced by mechanical factors.

Integrated Portable and Stationary Health Impact-Monitoring System for Firefighters.

The multi-layered negative effects caused by pollutants released into the atmosphere as a result of fires served as the stimulus for the development of a system that protects the health of firefighters operating in the affected area. A collaborative network comprising mobile and stationary Internet of Things (IoT) devices that are furnished with gas sensors, along with a remote server, constructs a resilient framework that monitors the concentrations of harmful emissions, characterizes the ambient air quality of the vicinity where the fire transpires, adopting European Air Quality levels, and communicates the outcomes via suitable applications (RESTful APIs and visualizations) to the stakeholders responsible for fire management decision making. Different experimental evaluations adopting separate contexts illustrate the operation of the infrastructure.

A chemo-mechanical model of endoderm movements driving elongation of the amniote hindgut.

Although mechanical and biochemical descriptions of development are each essential, integration of upstream morphogenic cues with downstream tissue mechanics remains understudied during vertebrate morphogenesis. Here, we developed a two-dimensional chemo-mechanical model to investigate how mechanical properties of the endoderm and transport properties of fibroblast growth factor (FGF) regulate avian hindgut morphogenesis in a coordinated manner. Posterior endoderm cells convert a gradient of FGF ligands into a contractile force gradient, leading to a force imbalance that drives collective cell movements that elongate the forming hindgut tube. We formulated a 2D reaction-diffusion-advection model describing the formation of an FGF protein gradient as a result of posterior displacement of cells transcribing unstable Fgf8 mRNA during axis elongation, coupled with translation, diffusion and degradation of FGF protein. The endoderm was modeled as an active viscous fluid that generates contractile stresses in proportion to FGF concentration. With parameter values constrained by experimental data, the model replicates key aspects of hindgut morphogenesis, suggests that graded isotropic contraction is sufficient to generate large anisotropic cell movements, and provides new insight into how chemo-mechanical coupling across the mesoderm and endoderm coordinates hindgut elongation with axis elongation.

A chemo-mechanical model of endoderm movements driving elongation of the amniote hindgut.

While mechanical and biochemical descriptions of development are each essential, integration of upstream morphogenic cues with downstream tissue mechanics remains understudied in many contexts during vertebrate morphogenesis. A posterior gradient of Fibroblast Growth Factor (FGF) ligands generates a contractile force gradient in the definitive endoderm, driving collective cell movements to form the hindgut. Here, we developed a two-dimensional chemo-mechanical model to investigate how mechanical properties of the endoderm and transport properties of FGF coordinately regulate this process. We began by formulating a 2-D reaction-diffusion-advection model that describes the formation of an FGF protein gradient due to posterior displacement of cells transcribing unstable Fgf8 mRNA during axis elongation, coupled with translation, diffusion, and degradation of FGF protein. This was used together with experimental measurements of FGF activity in the chick endoderm to inform a continuum model of definitive endoderm as an active viscous fluid that generates contractile stresses in proportion to FGF concentration. The model replicated key aspects of hindgut morphogenesis, confirms that heterogeneous - but isotropic - contraction is sufficient to generate large anisotropic cell movements, and provides new insight into how chemo-mechanical coupling across the mesoderm and endoderm coordinates hindgut elongation with outgrowth of the tailbud.

Modeling the sensitivity of cyanobacteria blooms to plausible changes in precipitation and air temperature variability.

Many recent studies have attributed the observed variability of cyanobacteria blooms to meteorological drivers and have projected blooms with worsening societal and ecological impacts under future climate scenarios. Nonetheless, few studies have jointly examined their sensitivity to projected changes in both precipitation and temperature variability. Using an Integrated Assessment Model (IAM) of Lake Champlain's eutrophic Missisquoi Bay, we demonstrate a factorial design approach for evaluating the sensitivity of concentrations of chlorophyll a (chl-a), a cyanobacteria surrogate, to global climate model-informed changes in the central tendency and variability of daily precipitation and air temperature. An Analysis of Variance (ANOVA) and multivariate contour plots highlight synergistic effects of these climatic changes on exceedances of the World Health Organization's moderate 50 µg/L concentration threshold for recreational contact. Although increased precipitation produces greater riverine total phosphorus loads, warmer and drier scenarios produce the most severe blooms due to the greater mobilization and cyanobacteria uptake of legacy phosphorus under these conditions. Increases in daily precipitation variability aggravate blooms most under warmer and wetter scenarios. Greater temperature variability raises exceedances under current air temperatures but reduces them under more severe warming when water temperatures exceed optimal values for cyanobacteria growth more often. Our experiments, controlled for wind-induced changes to lake water quality, signal the importance of larger summer runoff events for curtailing bloom growth through reductions of water temperature, sunlight penetration and stratification. Finally, the importance of sequences of wet and dry periods in generating cyanobacteria blooms motivates future research on bloom responses to changes in interannual climate persistence.

The role of loading in murine models of rotator cuff disease.

Rotator cuff disease pathogenesis is associated with intrinsic (e.g., age, joint laxity, muscle weakness) and extrinsic (e.g., mechanical load, fatigue) factors that lead to chronic degeneration of the cuff tissues. However, etiological studies are difficult to perform in patients due to the long duration of disease onset and progression. Therefore, the purpose of this study was to determine the effects of altered joint loading on the rotator cuff. Mice were subjected to one of three load-dependent rotator cuff tendinopathy models: underuse loading, achieved by injecting botulinum toxin-A into the supraspinatus muscle; overuse loading, achieved using downhill treadmill running; destabilization loading, achieved by surgical excision of the infraspinatus tendon. All models were compared to cage activity animals. Whole joint function was assessed longitudinally using gait analysis. Tissue-scale structure and function were determined using microCT, tensile testing, and histology. The molecular response of the supraspinatus tendon and enthesis was determined by measuring the expression of 84 wound healing-associated genes. Underuse and destabilization altered forepaw weight-bearing, decreased tendon-to-bone attachment strength, decreased mineral density of the humeral epiphysis, and reduced tendon strength. Transcriptional activity of the underuse group returned to baseline levels by 4 weeks, while destabilization had significant upregulation of inflammation, growth factors, and extracellular matrix remodeling genes. Surprisingly, overuse activity caused changes in walking patterns, increased tendon stiffness, and primarily suppressed expression of wound healing-related genes. In summary, the tendinopathy models demonstrated how divergent muscle loading can result in clinically relevant alterations in rotator cuff structure, function, and gene expression.

Water acquisition and use during unconventional oil and gas development and the existing data challenges: Weld and Garfield counties, CO.

Colorado has recently experienced a significant increase in unconventional oil and gas development, with the greatest concentration of activity occurring in Weld and Garfield counties. Water for oil and gas development has received much attention mainly because water resources are limited in these regions and development is taking place closer to populated areas than it did in the past. Publicly available datasets for the period 2011-2014 were used to identify water acquisition strategies and sources of water used for oil and gas. In addition, the annual average water used in these two counties was quantified and compared to their total water withdrawals. The analysis also quantified the water needed for different well types, along with the flowback water that is retrieved. Weld and Garfield counties are dissimilar in respect to development practices for water acquisition, preferred well type and the fate of flowback water. But at the same time, this difference displays how geological characteristics, water availability, and administration localities are the key elements along with economics in the decision making process within the oil and gas sector. This effort also revealed data challenges regarding accessibility and reliability of reported information, and the need for additional data. Improving the understanding of the unconventional oil and gas sector's water use will help identify possible effects and tradeoffs on the local/regional level, which could diminish the conflicting perspectives that shape the water-energy discussions. This would complement the ability to make informed water resources planning and management decisions that are environmentally and socially acceptable.

Relapsing Episodes of Loss of Consciousness in a Patient With Hepatocellular Carcinoma.

Hypoglycemia is common in people with diabetes treated with insulin or oral medications such as sulphonylureas or other secretagogues, and constitutes a relatively rare paraneoplastic syndrome in patients with a variety of mesenchymal or epithelial tumors. In this case report we present a 51-year-old patient with metastatic hepatocellular carcinoma and persistent, severe, symptomatic hypoglycemia and we discuss management options and review the relevant medical literature.

Coexistence of Crohn's disease in a patient with systemic lupus erythematosus.

The concurrence of inflammatory bowel disease with systemic lupus erythematosus (SLE) is rare. The concomitant diagnosis of Crohn's disease and SLE is even more rare. The patient, a 40-year-old woman, was admitted to our hospital because of relapsing episodes of abdominal pain, diarrheas upper and lower extremities arthralgias, Raynaud's phenomenon with positive antinuclear antibodies, and fever for the last 2 years. The patient was diagnosed elsewhere with SLE and treated with hydroxychloroquine. Her medical history also included tonsillectomy and total hip replacement after a car accident. Family history was unremarkable. Physical examination was unremarkable except of very mild pain at lower left abdominal quadrant. Laboratory tests showed erythrocyte sedimentation rate at 32 mm/h, C-reactive protein at 36 mg/dl, positive rheumatoid factor, and increased C3, C4, positive antinuclear antibodies with the presence of anti-Sm and anti-RNP antibodies. Ileocolonoscopy revealed colonic inflammation with ulcers and pseudopolyps. Subsequent biopsies were diagnostic of Crohn's disease. Patient was diagnosed with Crohn's colitis concomitant to systemic lupus erythematosus and was started on therapy with azathioprine 2 mg/Kg, methylprednisolone 16 mg/d with slow tapering, mesalazine 1.5 g/day, and hydroxychloroquine. Patient is in excellent health status on the six-month follow-up.